Intracranial EEG to Test How Noninvasive Stimulation Affects Hippocampal-dependent Memory

February 2, 2026 updated by: University of Chicago
Human intracranial electroencephalography (EEG) can provide brain-activity correlates of memory with high spatial and temporal resolution. This project will test functional relevance of these neural signals for memory behavioral performance using a novel noninvasive stimulation method. Findings will advance understanding of brain mechanisms for memory, as is needed to accelerate progress in the treatment of memory disorders.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Enrolling by invitation

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This exploratory project merges noninvasive brain stimulation with invasive/neurosurgical electrophysiological recordings in humans to identify mechanisms for how stimulation targeting the hippocampal network affects episodic memory performance. Hippocampal network dysfunction is associated with episodic memory impairments in a variety of neurologic and psychiatric disorders. Core regions of this network such as the hippocampus are too deep within the brain to be directly affected by well-validated noninvasive neuromodulation approaches. Hippocampal Indirectly Targeted Stimulation ("HITS") addresses this limitation by targeting the hippocampus indirectly via stimulation-accessible neocortical hippocampal-network locations, to which patterned transcranial magnetic stimulation is applied. HITS reliably improves episodic memory performance and increases fMRI activity of the hippocampal network, including the hippocampus. However, it is not clear how HITS affects neural activity to produce these effects. Memory performance is supported by spatiotemporally coordinated neural activity of the hippocampal network, such as in synchronization of thetafrequency band oscillatory activity. The investigators hypothesize that HITS directly influences this coordinated activity within the hippocampal network. Alternatively, HITS could have a variety of nonspecific, indirect, or neuromodulatory effects that are not necessarily specific to the hippocampal network. Intracranial EEG (iEEG) recorded from multi-contact depth macroelectrodes in patients undergoing neurosurgical procedures provides the required temporal and spatial precision needed to test the hypothesis that HITS directly impacts hippocampal network activity. The investigators therefore will perform HITS in patients undergoing iEEG. The investigators will determine the impact of HITS on activity of the hippocampal network versus on off-target brain areas. To test whether HITS influences the coordination of theta-band oscillatory activity that is especially important for memory, the investigators will use a stimulation rhythm that should maximally affect this activity (theta-burst patterned stimulation) versus control rhythms and will administer HITS during a memory task versus during task-free periods. This is an ideal exploratory project because HITS-iEEG has a strong scientific rationale but involves many technical and logistical challenges yet to be solved. Success could motivate highly impactful research using HITS-iEEG. For example, understanding neural mechanisms of how HITS improves episodic memory could illuminate how to achieve memory enhancement via other methods, such as by deep-brain stimulation, by portable noninvasive electrical stimulation methods, or by next-generation noninvasive stimulation technologies. This future research would have strong scientific potential, in providing stimulation-based causal tests of brain-behavior relationships for memory. Findings could motivate brain stimulation therapy for neurological and psychiatric memory disorders.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University Of Chicago Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 18+ years old
  • Native English speakers
  • Normal or corrected-to-normal near and far vision

Exclusion Criteria:

-iEEG electrode placement in area of parietal lobe that will interfere with placement of TMS coil for HITS stimulation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Single pulse TMS stimulation
The investigators will measure neural activity evoked by single pulses of Hippocampal Indirectly Targeted Stimulation (HITS). Stimulation intensity will vary to yield dose-response information. The investigators will also stimulate a control location. The investigators hypothesize that hippocampus/hippocampal-network intracranial EEG (iEEG) activity will respond to HITS, but not to control-location stimulation. Moreover, the selectivity of EPs will vary with HITS intensity, with very high intensities yielding less-selective (off-target) EP responses outside the hippocampal network. Findings consistent with these hypotheses would indicate that HITS directly impacts hippocampal and/or hippocampal-network neural activity
Other: Transcranial magnetic stimulation (TMS)
Study conditions will involve different parameters for electrical stimulation delivered using non-invasive TMS.
Experimental: Theta-burst TMS stimulation
During task-free periods (fixation cross), HITS will be delivered in a theta-burst rhythm, versus two control non-theta rhythms and no-stimulation control. The investigators will test whether HITS entrains theta in the period immediately following 2-s trains of each condition. The investigators hypothesize that theta-burst HITS will entrain endogenous hippocampal and hippocampal-network theta more than control stimulation. Stimulation will also be delivered within a memory encoding task using naturalistic visual scenes. The investigators hypothesize that hippocampal theta entrainment by HITS will significantly increase during encoding relative to task-free periods, and that this effect will be selective versus the control stimulation conditions. Further, the investigators hypothesize that theta-burst HITS will improve memory relative to the control conditions. Such findings would indicate that HITS influences memory-related hippocampal theta activity.
Other: Transcranial magnetic stimulation (TMS)
Study conditions will involve different parameters for electrical stimulation delivered using non-invasive TMS.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Power of theta-band hippocampal electroencephalography (iEEG) activity
Time Frame: Measured while research activities are being completed, including during stimulation and the performance of the task . Measurement will take 2 to 4 hours on a single day.
Power of theta-band hippocampal iEEG activity will be recorded and used to measure local brain electrical activity evoked by task conditions
Measured while research activities are being completed, including during stimulation and the performance of the task . Measurement will take 2 to 4 hours on a single day.
Electroencephalography (iEEG) activity between hippocampus and the stimulated electrode
Time Frame: Measured while research activities are being completed, including during stimulation and the performance of the task . Measurement will take 2 to 4 hours on a single day.
iEEG is used to measure local brain electrical activity evoked by task conditions. iEEG will be recorded and analyzed to determine the synchrony of iEEG activity between hippocampus and the stimulated electrode.
Measured while research activities are being completed, including during stimulation and the performance of the task . Measurement will take 2 to 4 hours on a single day.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Chicago

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Joel Voss, PhD, University of Chicago

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 15, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 20, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 2, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 9, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 9, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 2, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB25-0756

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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